ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Glycoengineered Type II Anti-CD20 Monoclonal Antibody Pregnancy: Avoid — neonatal B-cell depletion reported with anti-CD20 in pregnancy; no specific obinutuzumab data; delay conception for 18 months after treatment.

Obinutuzumab (Anti-CD20 — Lupus Nephritis)

Brand names: Gazyvaro

Adult dose

Dose: Lupus nephritis (Phase 3 dose): 1000 mg IV on Days 1 and 15 (cycle 1); then 1000 mg IV on Day 1 of every subsequent 6-month cycle
Route: IV infusion (diluted — first infusion over ≥6 hours; subsequent over ≥4 hours)
Frequency: Every 6 months (maintenance after initial loading cycle)
Max: 1000 mg per infusion
Glycoengineered (obinutuzumab is type II anti-CD20 — differs from rituximab type I): causes more direct B-cell killing via ADCC/ADCP with less CDC; more complete and sustained B-cell depletion than rituximab. Currently licensed for CLL and follicular lymphoma (UK). NOBILITY trial showed benefit in lupus nephritis — FDA/MHRA approval for SLE indication pending (2024/2025).

Paediatric dose

Route:
Not currently licensed for LN indication in paediatrics.

Dose adjustments

Renal

No dose adjustment required for mild-moderate impairment.

Hepatic

No dose adjustment required.

Clinical pearls

  • NOBILITY trial (Jayne et al. NEJM 2022): obinutuzumab + MMF vs placebo + MMF in Class III/IV lupus nephritis — complete renal response at 52 weeks: 40% vs 23%; 76-week response: 35% vs 23% (sustained benefit). Significant improvement over rituximab historical data — greater B-cell depletion depth and duration may explain superiority
  • Type II vs Type I anti-CD20: rituximab is a type I anti-CD20 (redistributes CD20 into lipid rafts, activates CDC). Obinutuzumab is type II (CD20 not redistributed; 50× greater ADCC/ADCP activity; minimal CDC). Type II results in deeper and more sustained B-cell depletion — particularly relevant for LN where B-cell escape from rituximab is a clinical problem
  • HBV reactivation — MHRA black box: ALL patients must be screened for HBV before obinutuzumab; HBsAg+ patients must receive antiviral prophylaxis and viral monitoring throughout; HBcAb+/HBsAg-: prophylactic antiviral OR close monitoring; fatal HBV reactivation cases reported

Contraindications

  • Active hepatitis B (mandatory HBV screening; if HBsAg+ or HBcAb+, prophylactic antiviral required)
  • Active serious infection
  • Live vaccines

Side effects

  • Infusion-related reactions (very common first infusion — pre-medicate with antihistamine, glucocorticoid, paracetamol; slow infusion rate)
  • Infections (hypogammaglobulinaemia — monitor IgG; IVIG support)
  • Hepatitis B reactivation (fatal cases reported — strict pre-screening mandatory)
  • Progressive multifocal leukoencephalopathy (PML — rare but fatal; JC virus reactivation)
  • Tumour lysis syndrome (in lymphoma use — less relevant for LN)

Interactions

  • HBV — antiviral prophylaxis (entecavir or tenofovir) if HBcAb+ or HBsAg+
  • Live vaccines (absolute contraindication — no antibody response with B-cell depletion)
  • Chlorambucil (haematological combination in CLL — different from LN use)

Monitoring

  • HBV serology (HBsAg, HBcAb, HBV DNA) before each cycle
  • Serum IgG levels (hypogammaglobulinaemia — every 6 months)
  • Anti-dsDNA and complement (C3/C4) — SLE disease activity
  • Urinalysis and eGFR (renal response monitoring)
  • Neurological assessment (PML — new neurological symptoms)
  • Infusion monitoring (each infusion — IRR protocol)

Reference: BNFc; BNF 90; Jayne et al. NEJM 2022 (NOBILITY trial); MHRA Gazyvaro SPC; BSR SLE Guidelines 2023; FDA Breakthrough Therapy Designation for obinutuzumab in LN 2023. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways